Search Results (5,721)

Objective: This study aimed to investigate whether the subjective assessments of strong and weak muscles in the Functional Myodiagnosis muscle test (FMD-MT) can be objectively and reproducibly verified using physically measurable parameters. Additionally, we sought to evaluate the reliability of the manual muscle test in order to reinforce the scientific evidence supporting this accepted, yet not widely adopted, complementary medicine method. Methods: In a crossover observational study, three experienced medical practitioners conducted the FMD-MT of the rectus femoris muscle on 24 healthy participants using a specially designed therapy bench, with all measurements recorded via an oscillogram. The study investigated the force–time integral, joint angle change, additional force load, mean force turning point 1, as well as the interrater reliability and validity of both examiner assessments and instrumental analyses for the two muscle reaction variants: strong and weak. Results: A significant difference between the response pattern of strong and weak muscles was identified for the force–time integral (p = 0.005), the change in joint angle (p < 0.001), and the additional force load (p = 0.001). No difference between strong and weak muscles could be detected regarding the force turning point 1 (p = 0.972). The examiners demonstrated 100% accuracy in identifying weak muscle reactions as weak, and 99.2% accuracy in identifying strong muscle reactions as strong (p = 0.316). The overall intra-class correlation coefficient was 0.984. The oscillogram correctly visualized weak muscle reactions in weak muscles with an accuracy of 81.7%, and strong muscle reactions in strong muscles with an accuracy of 86.7% (p = 0.289). Conclusions: The Functional Myodiagnosis muscle test (FMD-MT) enables a clear and objective differentiation between strong and weak muscles, with statistically significant differences observed in the force–time integral, additional force load, and joint angle changes. Under rigorously standardized testing conditions, the FMD-MT of the rectus femoris muscle demonstrates a validity rate of 99.6% and an excellent reliability (ICC 0.984). Consequently, the FMD muscle test proves to be a reliable, reproducible, and objective diagnostic method. Trial registration: German Register of Clinical Studies U1111-1212-6622. Full article

Background: Attachments are essential components in clear aligner therapy, enhancing retention and improving the predictability of tooth movements. Mechanical and wear properties of the composite resins used for attachment reproduction are critical to maintaining their integrity and shape over time. This study aimed to evaluate and compare the mechanical properties, thermal behavior, and wear performance of the hybrid composite Aligner Connect (AC) and the flowable resin (Connect Flow, CF). Methods: Twenty samples (ten AC and ten CF) were reproduced. All specimens underwent differential scanning calorimetry (DSC), combustion analysis, flat instrumented indentation, compression stress relaxation tests, and tribological analysis. A 3D wear profile reconstruction was performed to assess wear surfaces. Results: DSC and combustion analyses revealed distinct thermal transitions, with CF showing significantly lower Tg values (103.8 °C/81.4 °C) than AC (110.8 °C/89.6 °C) and lower residual mass after combustion (23% vs. 61%), reflecting reduced filler content and greater polymer mobility. AC exhibited superior mechanical properties, with higher maximum load (585.9 ± 22.36 N) and elastic modulus (231.5 ± 9.1 MPa) than CF (290.2 ± 5.52 N; 156 ± 10.5 MPa). Stress relaxation decrease was less pronounced in AC (18 ± 4%) than in CF (20 ± 4%). AC also showed a significantly higher friction coefficient (0.62 ± 0.060) than CF (0.55 ± 0.095), along with greater wear volume (0.012 ± 0.0055 mm³ vs. 0.0070 ± 0.0083 mm³) and maximum depth (36.88 ± 3.642 µm vs. 17.91 ± 3.387 µm). Surface roughness before wear was higher for AC (Ra, 0.577 ± 0.035 µm; Rt, 4.369 ± 0.521 µm) than for CF (Ra, 0.337 ± 0.070 µm; Rt, 2.862 ± 0.549 µm). After wear tests, roughness values converged (Ra, 0.247 ± 0.036 µm for AC; Ra, 0.236 ± 0.019 µm for CF) indicating smoothened and similar surfaces for both composites. Conclusions: The hybrid nanocomposite demonstrated greater properties in terms of stiffness, load-bearing capacity, and structural integrity when compared with flowable resin. Its use may ensure more durable attachment integrity and improved aligner–tooth interface performance over time. Full article

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted on blood work or cerebrospinal fluid analysis. Tumor markers were within normal limits. As part of her diagnostic workup, a positron emission tomography (PET) scan was performed, which showed a highly FDG-avid solitary 7 mm left axillary lymph node. Ultrasound-guided percutaneous biopsy revealed metastatic poorly differentiated carcinoma. Histopathological examination could not conclusively distinguish between adenocarcinoma and squamous cell carcinoma. She was diagnosed with seronegative opsoclonus-myoclonus ataxia syndrome of paraneoplastic origin from an occult primary malignancy and started on pulsatile corticosteroids and intravenous immunoglobulin (IVIG), with only moderate symptomatic improvement. Given the anatomic location and immunohistochemical staining pattern of the lymph node, the malignancy was considered as being of primary breast origin. A left axillary lymph node dissection was performed, with 1/12 nodes testing positive for poorly differentiated carcinoma. The patient experienced significant improvement in her neurological symptoms 2–3 days following resection of the solitary malignant lymph node, largely regaining her functional independence. She went on to receive adjuvant radiotherapy to the breast and axilla, as well as adjuvant hormonal therapy. Full article

Stroke is a significant global health concern characterized by the abrupt disruption of cerebral blood flow, leading to neurological impairment. Accurate and timely diagnosis—enabled by imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI)—is essential for differentiating stroke types and initiating interventions like thrombolysis, thrombectomy, or surgical management. In parallel, recent advancements in wearable technology, particularly smart clothing, offer new opportunities for stroke prevention, real-time monitoring, and rehabilitation. These garments integrate various sensors, including electrocardiogram (ECG) electrodes, electroencephalography (EEG) caps, electromyography (EMG) sensors, and motion or pressure sensors, to continuously track physiological and functional parameters. For example, ECG shirts monitor cardiac rhythm to detect atrial fibrillation, smart socks assess gait asymmetry for early mobility decline, and EEG caps provide data on neurocognitive recovery during rehabilitation. These technologies support personalized care across the stroke continuum, from early risk detection and acute event monitoring to long-term recovery. Integration with AI-driven analytics further enhances diagnostic accuracy and therapy optimization. This narrative review explores the application of smart clothing in conjunction with traditional imaging to improve stroke management and patient outcomes through a more proactive, connected, and patient-centered approach. Full article

Background: Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their ability to secrete paracrine factors that modulate tissue repair. Extracellular vesicles (EVs) released by MSCs contain bioactive molecules (e.g., mRNAs, miRNAs, proteins) and play a key role in intercellular communication. Methods: This study compared the transcriptomic profiles (mRNA and miRNA) of equine MSCs derived from adipose tissue (AT-MSCs), bone marrow (BM-MSCs), and ovarian fibroblasts (as a differentiated control). Additionally, miRNAs present in EVs secreted by these cells were characterized using next-generation sequencing. Results: All cell types met ISCT criteria for MSCs, including CD90 expression, lack of MHC II, trilineage differentiation, and adherence. EVs were isolated using ultracentrifugation and validated with nanoparticle tracking analysis and flow cytometry (CD63, CD81). Differential expression analysis revealed distinct mRNA and miRNA profiles across cell types and their secreted EVs, correlating with tissue origin. BM-MSCs showed unique regulation of genes linked to early development and osteogenesis. EVs contained diverse RNA species, including miRNA, mRNA, lncRNA, rRNA, and others. In total, 227 and 256 mature miRNAs were detected in BM-MSCs and AT-MSCs, respectively, including two novel miRNAs per MSC type. Fibroblasts expressed 209 mature miRNAs, including one novel miRNA also found in MSCs. Compared to fibroblasts, 60 and 92 differentially expressed miRNAs were identified in AT-MSCs and BM-MSCs, respectively. Conclusions: The results indicate that MSC tissue origin influences both transcriptomic profiles and EV miRNA content, which may help to interpret their therapeutic potential. Identifying key mRNAs and miRNAs could aid in future optimizing of MSC-based therapies in horses. Full article

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy. Full article

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Plaque erosion (PE) is now recognized as a common and clinically significant cause of acute coronary syndromes (ACSs), accounting for up to 40% of cases. Unlike plaque rupture (PR), PE involves superficial endothelial loss over an intact fibrous cap and occurs in a low-inflammatory setting, typically affecting younger patients, women, and smokers with fewer traditional risk factors. The growing recognition of PE has been driven by high-resolution intracoronary imaging, particularly optical coherence tomography (OCT), which enables in vivo differentiation from PR. Identifying PE with OCT has opened the door to personalized treatment strategies, as explored in recent trials evaluating the safety of deferring stent implantation in selected cases in favor of intensive medical therapy. Given its unexpectedly high prevalence, PE is now recognized as a common pathophysiological mechanism in ACS, rather than a rare exception. This growing awareness underscores the importance of its accurate identification through OCT in clinical practice. Early recognition and a deeper understanding of PE are essential steps toward the implementation of precision medicine, allowing clinicians to move beyond “one-size-fits-all” models toward “mechanism-based” therapeutic strategies. This narrative review aims to offer an integrated overview of PE, tracing its epidemiology, elucidating the molecular and pathophysiological mechanisms involved, outlining its clinical presentations, and placing particular emphasis on diagnostic strategies with OCT, while also discussing emerging therapeutic approaches and future directions for personalized cardiovascular care. Full article

Endometriosis is a benign and often underdiagnosed condition that affects women of reproductive age, typically between 18 and 45 years. It can cause infertility and pain, including radicular pain and low back pain (LBP). The aim of this case report is to emphasize the importance of making a differential diagnosis when facing LBP and radicular symptoms. We report the case of a 17-year-old female patient, R.A., presented with a significant LBP (NPRS 8/10) radiating from her lumbar spine to her right buttock and occasionally to both legs, accompanied by weakness. She revealed exacerbation of pain during menstruation, despite being under hormonal contraceptive treatment. After three physiotherapy sessions that included education, manual therapy and exercise, the patient’s pain persisted so her physiotherapist recommended an evaluation in the emergency department, where standard radiography did not reveal any significant findings. Physiotherapy continued until the fifth session, when the patient agreed to undergo evaluation at a specialized endometriosis centre. Further investigations revealed endometriotic tissue on the uterosacral ligament, leading to hormonal therapy adjustment, with which pain gradually decreased to a manageable level (NPRS 2/10). This case report highlights the importance of an early differential diagnosis in patients with LBP, as endometriosis can present not only in older women but also in younger patients, including those already on oral contraceptives. Therefore, to mitigate the risk of pattern recognition bias, clinicians must maintain a high index of suspicion for endometriosis, even in atypical or unlikely clinical presentations. Full article